Inside this issueCover storiesA passionate ventureNew PET Center will aid drug developmentA 'country doctor' gives back to Yale by aiding studentsPartnershipsHigh school partnership celebrates 10 yearsGrants & contractsPeopleLifelines: Kenneth MillerCell-signaling expert will lead vascular biologyMedical oncologist is appointed deputy director of Cancer CenterImmunobiology chair is named to Institute of MedicineScientist is honored by foundation for research on lupusOut & aboutAwards & honorsScienceImmunology comes of age at medical schoolYale research makes Science's 'top 10' listAdvances: Breathing easier about lung injury? | Changes in Medicare help prevent cancers | Inclined by genes toward nicotine | Missing molecule puts neurons off track  
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AdvancesHealth and science news from YaleMissing molecule puts neurons off trackDuring fetal development, different types of neurons must journey to their proper place in the brain’s cerebral cortex. A wrong turn along the way may have devastating results, including periventricular heterotopia (PVH), a congenital brain malformation that can cause epilepsy, mental retardation and deficits in learning and memory. PVH is associated with mutations in a gene known as Filamin-A, but little has been known about how these mutations cause neurons to go astray. Research led by Pasko Rakic, M.D., Ph.D., professor and chair of neurobiology and director of Yale’s Kavli Institute for Neuroscience, has now implicated MEKK4, an intracellular signaling molecule that contributes to proper neuronal migration. In the December 7, 2006, issue of Neuron, Rakic’s team showed that MEKK4 regulates levels of Filamin-A protein in the developing brains of mice and that mice engineered to lack MEKK4 had impaired neuronal movement and an increased incidence of PVH. The findings shed new light on PVH and on cortical development, “a dynamic and complex process that, in humans, occurs during gestation over many months and is regulated by numerous molecules,” says Rakic. Breathing easier about lung injury?
Patients with heart or lung problems, including premature babies, are given supplemental oxygen. But this intervention is sometimes too much of a good thing, because prolonged high concentrations of oxygen can cause hyperoxic acute lung injury, or HALI, in which the lungs’ capillaries become leaky. The protein angiopoietin-2 (Ang2) destabilizes blood vessels, so Jack A. Elias, M.D., the Waldemar Von Zedtwitz Professor and chair of internal medicine, led a study to see whether Ang2 might contribute to HALI. In the November 5, 2006 issue of Nature Medicine, Elias’s team reported high Ang2 levels and greater cell death in fluids and lung tissue taken from mice, adult humans and premature infants after exposure to high oxygen levels. But mice treated with RNA that suppressed Ang2 expression had far less damage, and mice bred to lack Ang2 lived significantly longer than their counterparts, raising the possibility that drugs designed to curb Ang2 could protect patients against HALI. Vineet Bhandari, M.B.B.S., M.D., D.M., assistant professor of pediatrics and first author, says that the study was true bench-to-bedside research. “All the work was initially done on mice ... and then we showed its clinical relevance by documenting its presence in human patients with acute lung injury.” Inclined by genes toward nicotine
Nearly 5 million people die prematurely each year from diseases related to smoking. Yet the World Health Organization estimates that more than a billion people smoke, a testament to tobacco’s addictive nature. Growing evidence indicates that some of the tendency to develop nicotine dependence is inherited. Using DNA from smokers in African-American and European-American families, Joel Gelernter, M.D., professor of psychiatry, genetics and neurobiology, and colleagues recently linked several genetic regions to nicotine dependence. Many of these regions had already been targeted by other researchers, but in a new finding reported in the January issue of Biological Psychiatry, the Gelernter team has shown that a region of chromosome 5 that contains several genes is strongly associated to nicotine dependence in the African-Americans in the study. “These data add to the growing evidence for specific locations for genes that influence risk for nicotine dependence,” says Gelernter, who now hopes to zero in on the specific gene or genes that influence nicotine dependence. Changes in Medicare help prevent cancersWhen Medicare coverage expanded to include screening for colon cancer, early diagnosis and treatment also increased, according to a report by School of Medicine researchers in the December 20, 2006 issue of JAMA: The Journal of the American Medical Association. Medicare reimbursement rules first changed in 1998 to cover screening colonoscopies for patients at risk for colon cancer. In 2001 coverage was expanded to include all Medicare recipients. A team led by Cary P. Gross, M.D., associate professor of medicine, found that colonoscopies have increased by 600 percent since the first Medicare change. The percentage of patients diagnosed at an early stage increased from 22.5 percent to 25.5 percent since 1998; after 2001, that percentage rose to 26.3. “These data strongly support initiatives to increase access to and use of screening colonoscopy, yet more work needs to be done, as many eligible patients still are not receiving appropriate screening for colorectal cancer,” Gross says.  |
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